Substituted indazol-pyrrolopyrimidines useful in the treatment of hyperproliferative diseases

Abstract

The present invention relates to substituted indazol-pyrrolopyrimidine compounds of general formula (I): in which R 1a , R 1b , R 1c , R 1d , R 2a and R 2b are as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

1 . A compound of general formula I: 
       
         
           
           
               
               
           
         
         in which: 
         R 1a  represents a hydrogen atom or a halogen atom or a hydroxy-, cyano-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 3 -C 7 -cycloalkyloxy-, (3- to 10-membered heterocycloalkyl)-O—, —NR 5a R 5b , —SCF 3  or —SF 5  group; 
         R 1b  represents a hydrogen atom or a halogen atom or a hydroxy-, cyano-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 3 -C 7 -cycloalkyloxy-, (3- to 10-membered heterocycloalkyl)-O—, —NR 5a R 5b , —SCF 3  or —SF 5  group; 
         R 1c  represents a hydrogen atom or a halogen atom or a hydroxy-, cyano-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 3 -C 7 -cycloalkyloxy-, (3- to 10-membered heterocycloalkyl)-O—, —NR 5a R 5b , —SCF 3  or —SF 5  group; 
         R 1d  represents a hydrogen atom or a halogen atom or a hydroxy-, cyano-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 3 -C 7 -cycloalkyloxy-, (3- to 10-membered heterocycloalkyl)-O—, —NR 5a R 5b , —SCF 3  or —SF 5  group; 
         with the proviso that R 1a , R 1b , Ric and R 1d  do not represent a hydrogen atom simultaneously; 
         R 2a  represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-, cyano-, —(CH 2 ) q —X—(CH 2 ) p —R 3 ; wherein said C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups; 
         R 2b  represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-, cyano-, —(CH 2 ) q —X—(CH 2 ) p —R 3 ; wherein said C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups; 
         X represents a bond or a bivalent group selected from: —O—, —S—, —S(═O)—, —S(═O) 2 —, —S(═O)—(NR 3a )—, —(NR 3a )—S(═O)—, —C(═O)—, —(NR 3a )—, —C(═O)—O—, —O—C(═O)—, —C(═S)—O—, —O—C(═S)—, —C(═O)—(NR 3a )—, —(NR 3a )—C(═O)—, —(NR 3a )—C(═O)—(NR 3b )—, —O—C(═O)—(NR 3a )—, —(NR 3a )—C(═O)—O—; 
         R 3  represents a hydrogen atom or a group selected from C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-; said groups being optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups; 
         R 3a  represents a hydrogen atom or a group selected from C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-; said groups being optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups; 
         R 3b  represents a hydrogen atom or a group selected from C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-; said groups being optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups; 
         or 
         R 3  together with R 3a  or R 3b  represent a 3- to 10-membered heterocycloalkyl- or a 4- to 10-membered heterocycloalkenyl- group, which is optionally substituted, one or more times, identically or differently, with halo-, hydroxyl- or cyano-; 
         R 4  represents halo-, hydroxy-, oxo- (O═), cyano-, nitro-, C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, halo-C 6 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, hydroxy-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, R 5 —O—, —C(═O)—R 5 , —C(═O)—O—R 5 , —O—C(═O)—R 5 , —N(R 5a )—C(═O)—R 5b , —N(R 5a )—C(═O)—NR 5b R 5c , —NR 5a R 5b , —C(═O)—NR 5a R 5b , R 5 —S—, R 5 —S(═O)—, R 5 —S(═O) 2 —, —N(Ra)—S(═O)—R 5b , —S(═O)—NR 5a R 5b , —N(R 5a )—S(═O) 2 —R 5b , —S(═O) 2 —NR 5a R 5b , —S(═O)(═NR 5a )R 5b , —S(═O)(═NR 5a )R 5b  or —N═S(═O)(R 5a )R 5b ; 
         R 5  represents a hydrogen atom, a C 1 -C 6 -alkyl- or C 3 -C 6 -cycloalkyl- group; 
         R 5a  represents a hydrogen atom, or a group selected from: C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, aryl-(CH 2 ) r —, heteroaryl-(CH 2 ) r —; 
         R 5b  represents a hydrogen atom, a C 1 -C 6 -alkyl- or C 3 -C 6 -cycloalkyl- group; 
         R 5c  represents a hydrogen atom, a C 1 -C 6 -alkyl- or C 3 -C 6 -cycloalkyl- group; 
         or 
         R 5a  and R 5b , 
         or R 5a  and R 5c , 
         or R 5b  and R 5c  together form a C 2 -C 6 -alkylene group, in which optionally one methylene is replaced by —O—, —C(═O)—, —NH—, or —N(C 1 -C 4 -alkyl)-; 
         p represents an integer of 0, 1, 2 or 3; 
         q represents an integer of 0, 1, 2 or 3; 
         r represents an integer of 0, 1 or 2; 
         or a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same; 
         wherein the following compounds are excluded: 
         4-[4-[[7-[2-(dimethylamino)ethyl]-1H-indazol-5-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         4-[4-[[7-[(dimethylamino)methyl]-1H-indazol-5-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         4-[4-[(3-amino-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         4-[4-[[7-[2-(dimethylamino)ethyl]-1H-indazol-5-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-N-(1,1-dimethylethyl)-3,6-dihydro-1(2H)-pyridinecarboxamide, 
         3,6-dihydro-4-[4-[(3-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-1 (2H)-Pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         1-[4-[4-[(3-chloro-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-1(2H)-pyridinyl]-3-(1-piperidinyl)-1-propanone, 
         4-[4-[[7-[(dimethylamino)methyl]-1H-indazol-5-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-N-(1,1-dimethylethyl)-3,6-dihydro-1(2H)-pyridinecarboxamide, 
         4-[4-[(3-chloro-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         1-[3,6-dihydro-4-[4-[(3-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-1(2H)-pyridinyl]-3-(1H-imidazol-1-yl)-1-propanone, 
         4-[4-[[7-(aminomethyl)-1H-indazol-5-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         4-[4-[(3-ethyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         4-[4-[[7-(aminomethyl)-1H-indazol-5-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-N-(1,1-dimethylethyl)-3,6-dihydro-1(2H)-pyridinecarboxamide, 
         3,6-dihydro-4-[4-[(6-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-1 (2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         1-[3,6-dihydro-4-[4-[(3-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-1(2H)-pyridinyl]-3-(1-piperidinyl)-1-propanone, 
         3,6-dihydro-4-[4-[(3-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-1 (2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester, 
         1-[3,6-dihydro-4-[4-[(3-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-1(2H)-pyridinyl]-3-(dimethylamino)-1-propanone, 
         N-(3-chloro-1H-indazol-5-yl)-6-(1,2,3,6-tetrahydro-4-pyridinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tris hydrochloride, 
         N-(3-chloro-1H-indazol-5-yl)-6-(1,2,3,6-tetrahydro-4-pyridinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride, 
         N-(3-chloro-1H-indazol-5-yl)-6-(1,2,3,6-tetrahydro-4-pyridinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine, 
         N-(3-methyl-1H-indazol-5-yl)-6-(1,2,3,6-tetrahydro-4-pyridinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tris hydrochloride, 
         N-(3-methyl-1H-indazol-5-yl)-6-(1,2,3,6-tetrahydro-4-pyridinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine, 
         5-[(4-amino-1-piperidinyl)methyl]-N-1H-indazol-5-yl-7H-pyrrolo[2,3-d]pyrimidin-4-amine, 
         4-[4-(1-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid (2-methoxy-1,1-dimethylethyl)-amide, 
         4-[4-(1-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid (2-dimethylamino-1,1-dimethylethyl)-amide, 
         4-[4-(1-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid (1,1-dimethyl-2-pyrrolidin-1-ylethyl)-amide, 
         4-[4-(1-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid (1,1-dimethyl-2-morpholin-4-ylethyl)-amide, 
         4-[4-(1H-Indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester, 
         4-[4-(3-Chloro-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester, 
         1-{4-[4-(3-Chloro-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridin-1-yl}-3-piperidin-1-yl-propan-1-one, 
         (3-Chloro-1H-indazol-5-yl)-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine tris-hydrochloride, 
         4-[4-(3-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester, 
         3-Methyl-1H-indazol-5-yl)-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine tris-hydrochloride, 
         3-Dimethylamino-1-4-[4-(3-methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridin-1-ylpropan-1-one, 
         3-Imidazol-1-yl-1-{4-[4-(3-methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridin-1-yl}-propan-1-one, 
         4-[4-(3-Methoxy-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester, 
         (1-Methyl-1H-indazol-5-yl)-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine tris-hydrochloride, 
         4-[4-(1-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butylamide, 
         1-{4-[4-(1-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridin-1-yl}-3-piperidin-1-yl-propan-1-one, 
         2-(2-Methoxyethoxy)-1-{4-[4-(1-methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridin-1-yl}-ethanone, 
         {4-[4-(1-Methyl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridin-1-yl}-(4-methylpiperazin-1-yl)methanone, 
         N 4 -[3-(1-benzothiophen-2-yl)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine, 
         N-[7-(1-benzothiophen-2-yl)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine, 
         N 4 -[7-(1-benzothiophen-2-yl)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine, 
         2-amino-4-{[7-(1-benzothiophen-2-yl)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile, and 
         2-amino-4-{[7-(1-benzothiophen-2-yl)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. 
       
     
     
         2 . A compound according to  claim 1 , or a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same; wherein R 2a  is not any one of the following groups: 
       
         
           
           
               
               
           
         
         in which 
         z represents heteroaryl, —(C 1 -C 6 -alkylene)-O—(C 1 -C 6 -alkyl), —(C 0 -C 6 -alkylene)-(heterocyclyl), (C 0 -C 6 -alkylene)-(heteroaryl), —C(═O)—(C 0 -C 6 -alkyl), —C(═O)—(C 0 -C 6 alkylene)-O—(C 0 -C 6 -alkyl), —C(═O)—(C 0 -C 6 -alkylene)-O—(C 1 -C 6 -alkylene)-O—(C 0 -C 6 -alkyl), —C(═O)—(C 0 -C 6 -alkylene)-N(C 0 -C 6 -alkyl)(C 0 -C 6 alkyl), —C(═O)—(C 0 -C 6 -alkylene)-(heterocyclyl), —C(═O)—(C 0 -C 6 -alkylene)-(heterocyclyl)-C(═O)—(C 0 -C 6 -alkyl), —C(═O)—(C 0 -C 6 -alkylene)-(heteroaryl), —S(═O) 2 —(C 0 -C 6 -alkyl), —S(═O) 2 —N(C 0 -C 6 -alkyl)(C 0 -C 6 -alkyl), or —S(═O) 2 -(heteroaryl); wherein any of the alkyl, alkylene, heterocyclyl or heteroaryl optionally is substituted, identically or differently, with 1, 2, 3, 4, 5, or 6 substituents selected from: halo, OH, —(C 0 -C 6 -alkylene)-O—(C 0 -C 6 -alkyl), —(C 0 -C 6 -alkylene)-N(C 0 -C 6 -alkyl)(C 0 -C 6 -alkyl), —C(═O)—(C 0 -C 6 -alkylene)-N(C 0 -C 6 -alkyl)(C 0 -C 6 -alkyl), —C(═O)—(C 0 -C 6 -alkylene)-(heterocyclyl), or —C 1 -C 6 -alkyl; 
         or 
         z represents a group selected from: 
       
       
         
           
           
               
               
           
         
         wherein the piperazine or morpholine moieties are optionally substituted, identically or differently, with 1, 2, 3, 4, 5, or 6 C 1 -C 6 -alkyl groups. 
       
     
     
         3 . A compound of general formula I according to  claim 1   in which:   R 1a  represents a halogen atom or a C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 3 -C 7 -cycloalkyloxy- or (3- to 10-membered heterocycloalkyl)-O— group;   R 1b  represents a hydrogen atom;   R 1c  represents a hydrogen atom;   R 1d  represents a hydrogen atom;   R 2a  represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-, cyano-, —(CH 2 ) q —X—(CH 2 ) p —R 3 ;
 wherein said C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups; 
   R 2b  represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-, cyano-, —(CH 2 ) q —X—(CH 2 ) p —R 3 ;
 wherein said C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups; 
   X represents a bond or a bivalent group selected from: —O—, —S—, —S(═O)—, —S(═O) 2 —, —S(═O)—(NR 3a )—, —(NR 3a )—S(═O)—, —C(═O)—, —(NR 3a )—, —C(═O)—O—, —O—C(═O)—, —C(═S)—O—, —O—C(═S)—, —C(═O)—(NR 3a )—, —(NR 3a )—C(═O)—, —(NR 3a )—C(═O)—(NR 3b )—, —O—C(═O)—(NR 3a )—, —(NR 3a )—C(═O)—O—;   R 3a , R 3b  are the same or different and are independently selected from R 3 ;   R 3  represents a hydrogen atom or a group selected from C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, halo-C 1 -C 3 -alkyl-; said groups being optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R 4  groups;   or   R 3  together with R 3a  or R 3b  represent a 3- to 10-membered heterocycloalkyl- or a 4- to 10-membered heterocycloalkenyl- group, which is optionally substituted, one or more times, identically or differently, with halo-, hydroxyl- or cyano-;   R 4  represents halo-, hydroxy-, oxo- (O═), cyano-, nitro-, C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, halo-C 6 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, hydroxy-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, R 5 —O—, —C(═O)—R 5 , —C(═O)—O—R 5 , —O—C(═O)—R 5 , —N(R 5a )—C(═O)—R 5b , —N(R 5a )—C(═O)—NR 5b R 5c , —NR 5a R 5b , —C(═O)—NR 5a R 5b , R 5 —S—, R 5 —S(═O)—, R 5 —S(═O) 2 —, —N(R 5a )—S(═O)—R 5b , —S(═O)—NR 5a R 5b , —N(R 5a )—S(═O) 2 —R 5b , —S(═O) 2 —NR 5a R 5b , —S(═O)(═NR 5a )R 5b , —S(═O)(═NR 5a )R 5b  or —N═S(═O)(R 5a )R 5b ;   R 5a , R 5b , R 5c  are the same or different and are independently selected from R 5 ;   R 5  represents a hydrogen atom, a C 1 -C 6 -alkyl- or a C 3 -C 6 -cycloalkyl- group;   or   R 5a  and R 5b ,   or R 5a  and R 5c ,   or R 5b  and R 5c  together form a C 2 -C 6 -alkylene group, in which optionally one methylene is replaced by —O—, —C(═O)—, —NH—, or —N(C 1 -C 4 -alkyl)-;   p represents an integer of 0, 1, 2 or 3;   q represents an integer of 0, 1, 2 or 3;   or a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.   
     
     
         4 . A compound according to  claim 1 , wherein one of R 2a  and R 2b  represents a group selected from: —(CH 2 ) q —X—(CH 2 ) p —R 3 , C 3 -C 6 -cycloalkyl-, 3- to 0-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-; wherein said C 3 -C 6 -cycloalkyl-, 3- to 10-membered heterocycloalkyl- or 4- to 10-membered heterocycloalkenyl- is optionally substituted, identically or differently, with 1, 2 or 3 R 4  groups; and the other one of R 2a  and R 2b  represents a hydrogen atom or a halogen atom or a group selected from: C 1 -C 6 -alkyl-, halo-C 1 -C 3 -alkyl-, cyano-;
 or a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same. 
 
     
     
         5 . A compound according to  claim 1 , wherein
 X represents a bond or a bivalent group selected from: —C(═O)—, —C(═O)—O—, —C(═O)—(NR 3a )—, —(NR 3a )—C(═O)—, —(NR 3a )—C(═O)—(NR 3b )—, —O—C(═O)—(NR 3a )—, —(NR 3a )—C(═O)—O—;   R 3  represents a hydrogen atom or a group selected from C 1 -C 3 -alkyl-, 4- to 6-membered heterocycloalkyl-; wherein said C 1 -C 3 -alkyl- or 4- to 6-membered with one R 4  group;   R 3a  represents a hydrogen atom or a C 1 -C 3 -alkyl- group; wherein said C 1 -C 3 -alkyl- group is optionally substituted with one R 4  group;   R 3a  represents a hydrogen atom or a C 1 -C 3 -alkyl- group;   p represents an integer of 0 or 1; and   q represents an integer of 0 or 1.   
     
     
         6 . A compound according to  claim 1 , which is selected from the group consisting of:
 6-ethyl-N-(6-methoxy-1H-indazol-5-yl)-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   5-fluoro-N-(6-methoxy-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid,   {4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}(4-methylpiperazin-1-yl)methanone,   N-isopropyl-4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,   N-[3-(trifluoromethyl)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   4-[(6-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid,   5-fluoro-N-(6-fluoro-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   4-[(6-fluoro-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid,   5-fluoro-N-(6-methyl-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N,N-dimethyl-4-[(6-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,   {4-[(6-methyl-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}(4-methylpiperazin-1-yl)methanone,   4-[(6-methyl-1H-indazol-5-yl)amino]-N-(propan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,   5-bromo-N-(6-fluoro-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   4-[(6-fluoro-1H-indazol-5-yl)amino]-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,   {4-[(6-fluoro-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}(4-methylpiperazin-1-yl)methanone,   4-[(6-fluoro-1H-indazol-5-yl)amino]-N-(propan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,   5-bromo-N-(6-methoxy-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride (1:1),   6-bromo-N-(6-methoxy-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-6-(methylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   3-{4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}prop-2-yn-1-ol,   3-{4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}propan-1-ol,   N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   5-fluoro-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   5-bromo-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine, hydrochloride (1:1),   6-ethyl-5-methyl-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   4-{[6-(propan-2-yloxy)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid hydrochloride (1:1),   (4-methylpiperazin-1-yl)(4-{[6-(propan-2-yloxy)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanone,   N,N-dimethyl-4-{[6-(propan-2-yloxy)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,   N-(propan-2-yl)-4-{[6-(propan-2-yloxy)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,   3-(4-{[6-(propan-2-yloxy)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidin-6-yl)prop-2-yn-1-ol,   3-(4-{[6-(propan-2-yloxy)-1H-indazol-5-yl]amino}-7H-pyrrolo[2,3-d]pyrimidin-6-yl)propan-1-ol,   4-[(6-isopropoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile,   4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile,   6-bromo-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   5-methyl-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine   6-chloro-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   6-chloro-N-(6-methoxy-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   ethyl 4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate,   5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-indazole-3-carbonitrile,   N-(6-ethoxy-1H-indazol-5-yl)-6-ethyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   5-ethyl-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-6-propyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   5-ethyl-N-(6-methoxy-1H-indazol-5-yl)-6-propyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   ethyl 5-bromo-4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate,   5-bromo-4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid,   N-(6-methoxy-1H-indazol-5-yl)-5-(trifluoromethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-6-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-6-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   6-(phenylsulfonyl)-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   6-[(4-methylphenyl)sulfonyl]-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   6-(methylsulfonyl)-N-[6-(propan-2-yloxy)-1H-indazol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   6-bromo-N-(6-fluoro-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   N-(6-methoxy-1H-indazol-5-yl)-6-(2-methylpropyl)-5-(propan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   5-ethyl-N-(6-methoxy-1H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,   {5-bromo-4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}(morpholin-4-yl)methanone,   5-bromo-4-[(6-methoxy-1H-indazol-5-yl)amino]-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide,   {5-bromo-4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}(piperidin-1-yl)methanone,   {5-Bromo-4-[(6-methoxy-1H-indazol-5-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}(pyrrolidin-1-yl)methanone, and   N-{2-[benzyl(methyl)amino]ethyl}-5-bromo-4-[(6-methoxy-1H-indazol-5-yl)amino]-N-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide;   or a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.   
     
     
         7 . A method of preparing a compound of general formula I according to  claim 1 , in which method an intermediate compound of general formula II: 
       
         
           
           
               
               
           
         
         in which R 1a , R 1b , R 1c , and R 1d  are as defined in  claim 1  is allowed to react with an intermediate compound of general formula III: 
       
       
         
           
           
               
               
           
         
         in which R 2a  and R 2b  are as defined in  claim 1 , LG represents a leaving group and PG represents a hydrogen atom or a protective group; 
         thus providing a compound of general formula I: 
       
       
         
           
           
               
               
           
         
         in which R 1a , R 1b , R 1c , R 1d , R 2a  and R 2b  are as defined in  claim 1 . 
       
     
     
         8 . (canceled) 
     
     
         9 . A pharmaceutical composition comprising a compound of general formula I, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, or a mixture of same, according to  claim 1 , and a pharmaceutically acceptable diluent or carrier. 
     
     
         10 . A pharmaceutical combination comprising:
 one or more first active ingredients selected from a compound of general formula I according to  claim 1 , and   one or more second active ingredients selected from chemotherapeutic anti-cancer agents.   
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . A method for the treatment of a disease of uncontrolled cell growth, proliferation or survival, an inappropriate cellular immune response, or an inappropriate cellular inflammatory response comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         14 . A compound of general formula III: 
       
         
           
           
               
               
           
         
         in which R 2a  and R 2b  are as defined in  claim 1 , LG represents a leaving group and PG represents a hydrogen atom or a protective group. 
       
     
     
         15 . (canceled) 
     
     
         16 . The method according to  claim 13 , wherein the uncontrolled cell growth, proliferation or survival, inappropriate cellular immune response, or inappropriate cellular inflammatory response is mediated by the MKNK-1 pathway. 
     
     
         17 . The method according to  claim 16 , wherein the disease of uncontrolled cell growth, proliferation or survival, inappropriate cellular immune response, or inappropriate cellular inflammatory response is a haematological tumour, solid tumour or metastases thereof. 
     
     
         18 . The method according to  claim 18 , wherein the haematological tumour, solid tumour or metastases thereof is selected from leukaemias and myelodysplastic syndrome, malignant lymphomas, head and neck tumours, brain tumours and brain metastases, tumours of the thorax, non-small cell and small cell lung tumours, gastrointestinal tumours, endocrine tumours, mammary and other gynaecological tumours, urological tumours, renal, bladder and prostate tumours, skin tumours, and sarcomas, and metastases thereof.